US Patent 4,221,778: Claim Scope, Expiration, and Patent Landscape for Drug-Resin Sustained-Release Formulations

US Patent 4,221,778 covers sustained-release pharmaceutical preparations based on drug-loaded ion-exchange resin particles. Its core combination requires four elements: a pharmacologically active drug, an ion-exchange resin complex, a swelling-retarding impregnating agent, and a water-permeable diffusion barrier. The patent issued in 1980 and, under the pre-URAA 17-year patent term applicable to the patent, expired no later than 1997. It therefore presents no current US blocking patent risk, although its claim structure remains relevant to freedom-to-operate analyses involving later drug-resin formulations.[1][2]

What does US Patent 4,221,778 claim?

The independent claim covers a pharmaceutical preparation containing:

Ion-exchange resin particles.
A pharmacologically active drug absorbed onto the resin.
An impregnating agent that retards resin swelling in water.
A water-permeable diffusion-barrier coating applied after treatment with the impregnating agent.

Claim 1 identifies five qualifying impregnating agents:

Polyethylene glycol
Propylene glycol
Mannitol
Lactose
Methylcellulose

Claims 2 through 8 narrow the formulation progressively. Claim 2 limits the impregnating agent to polyethylene glycol. Claim 3 adds an ethyl-cellulose coating. Claims 4 through 8 identify specific active ingredients.

Claim	Additional limitation	Practical scope
1	Any listed impregnating agent and any water-permeable diffusion barrier	Broad combination claim
2	Polyethylene glycol	Narrows the swelling-control agent
3	Ethyl cellulose coating	Narrows the diffusion barrier
4	Phenylpropanolamine	Specific drug embodiment
5	Dextromethorphan	Specific drug embodiment
6	Ephedrine	Specific drug embodiment
7	Pseudoephedrine	Specific drug embodiment
8	Phentermine	Specific drug embodiment

The claims are product or composition claims. They do not expressly claim a manufacturing process, a method of treating a patient, a dosing regimen, or a particular dissolution profile.

How broad is claim 1 of US 4,221,778?

Claim 1 is materially broader than claims 2 through 8 because it does not limit the drug to one of the five named actives and does not require polyethylene glycol or ethyl cellulose.

A formulation could fall within claim 1 if it uses:

Any pharmacologically active drug;
An ion-exchange resin capable of forming a drug-resin complex;
Any one of the five listed swelling-retarding agents; and
A water-permeable diffusion barrier.

The claim does not specify:

The chemical identity of the ion-exchange resin;
The drug-to-resin ratio;
Resin particle size;
The amount or molecular weight of the impregnating agent;
Coating thickness;
Coating weight gain;
Porosity;
Release duration;
Dissolution conditions;
Dosage form;
Tablet, capsule, suspension, or sachet presentation;
Manufacturing temperature or solvent system.

That omission creates broad literal claim coverage, but the functional wording imposes meaningful proof requirements. A patentee would need to establish that the resin was treated with an amount "sufficient to retard" swelling and that the coating was a water-permeable diffusion barrier. The claim does not require complete suppression of swelling. It requires a measurable reduction or retardation relative to untreated resin.

What technical elements are essential to infringement?

A potentially accused product would need to satisfy each limitation of at least one asserted claim. For claim 1, the central elements are cumulative.

Drug-resin complex

The drug must be absorbed onto ion-exchange resin particles to form drug-resin complex particles. A conventional matrix tablet in which drug is dispersed through a polymer matrix would not inherently satisfy this limitation. The claim is directed to an ionic or adsorption-based resin complex, not merely any controlled-release polymer system.

The record would likely focus on:

Resin identity and ionic functionality;
Whether the active drug is loaded onto the resin;
Evidence of ionic binding or adsorption;
Drug loading capacity;
Whether the resulting material remains particulate.

Swelling-retarding impregnation

The resin particles must be treated with one of the listed agents in an amount sufficient to retard swelling in water. The list appears closed for claim 1. A formulation using glycerol, sorbitol, or another agent would not literally satisfy the listed-agent limitation unless another claim-construction theory applied.

The functional phrase creates two technical questions:

Whether the agent was used to treat the resin particles rather than merely included elsewhere in the dosage form.
Whether the treatment retards swelling by the required amount.

Water-permeable diffusion barrier

The coating must permit water penetration while limiting drug diffusion. A completely impermeable coating would not satisfy the express requirement. A rapidly dissolving coating could also present a claim-scope issue if it does not operate as a diffusion barrier.

Claim 3 specifically requires ethyl cellulose. Ethyl cellulose is generally water-insoluble but can be formulated as a permeable membrane using coating thickness, porosity, plasticizers, or pore-forming components. The claim does not state the amount or grade of ethyl cellulose.

What formulations are specifically protected by claims 2 through 8?

Claims 2 through 8 create a narrower formulation family centered on polyethylene glycol and, for claims 3 through 8, ethyl cellulose.

Drug	Required under the claim	Claim status
Phenylpropanolamine	PEG-treated drug-resin complex with ethyl-cellulose diffusion barrier	Claim 4
Dextromethorphan	PEG-treated drug-resin complex with ethyl-cellulose diffusion barrier	Claim 5
Ephedrine	PEG-treated drug-resin complex with ethyl-cellulose diffusion barrier	Claim 6
Pseudoephedrine	PEG-treated drug-resin complex with ethyl-cellulose diffusion barrier	Claim 7
Phentermine	PEG-treated drug-resin complex with ethyl-cellulose diffusion barrier	Claim 8

Each species claim incorporates all limitations of claims 1 through 3. A product containing pseudoephedrine alone would not infringe claim 7 unless it also uses an ion-exchange resin complex, polyethylene glycol treatment, and an ethyl-cellulose water-permeable diffusion barrier.

The claims do not cover every sustained-release product containing these drugs. Conventional extended-release tablets, osmotic systems, coated pellets without ion-exchange resin, and polymer matrices would fall outside the literal claims if they lack the required resin-complex architecture.

When did US Patent 4,221,778 lose exclusivity?

US Patent 4,221,778 issued in 1980. Patents issued before the Uruguay Round Agreements Act generally received a term of 17 years from issuance, subject to applicable terminal disclaimers and statutory adjustments.[1][2]

Event	Date or period
Patent issued	1980
Ordinary pre-URAA term	17 years from issuance
Estimated ordinary expiration	1997
Current enforceability	Expired
Current US patent blocking risk	None from this patent

The patent’s expiration means that a manufacturer does not need a license from the original patent owner to practice the claimed formulation in the United States today. Expiration does not eliminate the relevance of the patent as prior art against later applications, technical disclosure, or a source of historical formulation disclosures.

What is the Orange Book status of US Patent 4,221,778?

US Patent 4,221,778 should not be treated as a current Orange Book barrier. The FDA Orange Book lists patents submitted for approved drug products and identifies relevant patent and exclusivity information associated with approved applications.[3]

The patent number alone does not establish that it was ever listed against a particular NDA. Even if it was listed historically, its expiration removes it as a current patent obstacle. The Orange Book status of a specific product must be evaluated by NDA, active ingredient, dosage form, strength, and listed patent status. The claims supplied do not identify an NDA, product brand, or approved dosage form.

The patent also does not create current regulatory exclusivity. Patent expiration and FDA regulatory exclusivity are separate legal mechanisms. A formulation could have been protected by an NDA-based exclusivity period even after the patent expired, but the patent itself supplies no current exclusivity.

Does US Patent 4,221,778 create Paragraph IV risk?

No current Paragraph IV risk arises from the expired patent.

A Paragraph IV certification is relevant when a generic applicant challenges a listed patent identified in the Orange Book for an approved reference product.[4] Because US Patent 4,221,778 expired decades ago, an applicant would not need to certify that the patent is invalid or will not be infringed in order to launch a product today.

Historically, a Paragraph IV dispute could have involved a product containing one of the named sympathomimetic or antitussive drugs if the patent had been listed against an NDA. The likely dispute issues would have included:

Whether the generic used an ion-exchange resin complex;
Whether the resin had been treated with polyethylene glycol or another listed agent;
Whether the coating was a water-permeable diffusion barrier;
Whether the formulation used ethyl cellulose;
Whether the product practiced the specific drug claim.

No present launch delay should be attributed to this patent.

What patent landscape surrounds drug-resin sustained-release technology?

The relevant patent landscape has several technical clusters.

Ion-exchange resin drug complexes

These patents generally concern binding a drug to an ion-exchange resin to create a particulate complex. The objective is to control release, improve taste masking, stabilize the active ingredient, or enable liquid and multiparticulate dosage forms.

Membrane-coated resin particles

A second cluster covers coating drug-resin particles with polymers such as ethyl cellulose, cellulose acetate, acrylic polymers, or other water-permeable membranes. The coating controls water ingress and drug diffusion.

Resin swelling control

US 4,221,778 distinguishes its claimed approach by treating the resin with an impregnating agent before applying the diffusion barrier. The claimed theory is that swelling control improves the performance and reproducibility of the outer coating.

Product-specific and formulation-specific patents

Later patents may claim:

Specific resin chemistries;
Particular drug-to-resin ratios;
Particle-size distributions;
Coating weight gains;
Pore-former concentrations;
Release profiles;
Taste-masked liquid suspensions;
Multiparticulate capsules;
Combination cold medicines;
Manufacturing processes.

A modern freedom-to-operate search therefore should not stop with the expired patent. It should review later US patent families that claim specific resin grades, coating compositions, release kinetics, and commercial dosage forms.

How strong was the patent estate for this technology?

The patent estate represented by US 4,221,778 was strong in breadth at the independent-claim level but narrow in practical product embodiments.

Its strengths were:

Broad coverage of any pharmacologically active drug in claim 1;
Five alternative swelling-retarding agents;
No specified resin chemistry;
No specified release duration;
No specified dosage form;
Functional coverage of the diffusion-barrier concept.

Its limitations were:

The claim requires a specific combination of resin complex, swelling-retarding treatment, and coating;
The impregnating-agent list is limited;
Claims 2 through 8 require progressively narrower features;
The patent does not cover all controlled-release products containing the named drugs;
The patent is expired.

Strength factor	Assessment
Independent-claim breadth	Broad
Chemical specificity	Low
Formulation specificity	Moderate
Proof burden	Meaningful, because of functional limitations
Current enforceability	None
Relevance to later patentability	Significant as prior-art disclosure
Current commercial leverage	None

What manufacturing and IP barriers remain after expiration?

The expired patent does not eliminate other technical barriers. A current manufacturer may still face:

Later patents covering a particular ion-exchange resin;
Patents on coating equipment or coating processes;
Patents on specific extended-release profiles;
Regulatory requirements for demonstrating bioequivalence;
Product-specific patents associated with a marketed NDA;
Trade-secret restrictions involving resin loading, coating uniformity, or scale-up;
Manufacturing controls for particle-size distribution and dissolution performance.

The expired patent’s disclosure may also make broad later claims difficult to obtain. A later applicant would likely need to claim a materially narrower improvement, such as a defined resin, coating ratio, release profile, or process condition, rather than the basic combination already disclosed in US 4,221,778.

Which companies are challenging US Patent 4,221,778?

No current challenger is required because the patent has expired. The supplied claim set does not identify any historical litigation, ANDA filer, licensee, settlement agreement, or patent owner beyond the patent document itself. A litigation conclusion cannot be attributed to the patent without a verified court docket or regulatory record.

The commercial competitive landscape is therefore defined by expired foundational IP and later formulation patents, not by active enforcement of US 4,221,778.

Key Takeaways

US Patent 4,221,778 claims drug-loaded ion-exchange resin particles treated to retard swelling and covered with a water-permeable diffusion barrier.
Claim 1 is broad because it does not limit the drug, resin chemistry, coating polymer, particle size, or dosage form.
Claims 2 through 8 narrow the invention to polyethylene glycol, ethyl cellulose, and five named drugs.
The patent issued in 1980 and expired under the pre-URAA 17-year term, no later than 1997.
It presents no current US infringement, Orange Book, Paragraph IV, or launch-blocking risk.
Its technical disclosure remains relevant prior art for later patents covering drug-resin complexes, membrane coatings, and swelling-control systems.
Current freedom-to-operate risk depends on later patents, approved-product listings, and formulation-specific rights rather than this patent.

FAQs About US Patent 4,221,778

Does US Patent 4,221,778 cover all extended-release pseudoephedrine products?

No. Claim 7 requires a pseudoephedrine drug-resin complex, polyethylene glycol treatment, and an ethyl-cellulose water-permeable diffusion barrier. Other extended-release pseudoephedrine technologies fall outside the claim if they lack those elements.

Can a company practice claim 4 today without a license?

Yes, the patent expired. A company must still evaluate later patents, regulatory requirements, and product-specific rights.

Is ethyl cellulose required for every claim?

No. Claim 1 allows any water-permeable diffusion barrier. Ethyl cellulose becomes mandatory only for claim 3 and its dependent claims 4 through 8.

Does the patent claim a method of treating cough, cold, or obesity?

No. The claims supplied are directed to pharmaceutical preparations. They do not claim a therapeutic method or dosing regimen.

Could a later patent validly claim the same basic formulation concept?

A broad claim repeating the disclosed combination would face substantial prior-art risk. A later patent would generally need a narrower, non-obvious improvement, such as a defined resin, coating architecture, process, or release profile.

References

U.S. Patent No. 4,221,778. (1980). Pharmaceutical preparation comprising drug-resin complex particles treated to retard swelling and coated with a diffusion barrier. United States Patent and Trademark Office.
35 U.S.C. § 154(c)(1). Patent term for pre-URAA patents.
U.S. Food and Drug Administration. (2025). Approved drug products with therapeutic equivalence evaluations. FDA.
21 U.S.C. § 355(j)(2)(A)(vii)(IV). Paragraph IV patent certification requirements.

Details for Patent: 4,221,778

Summary for Patent: 4,221,778